SPHK2 p.Pro380=
c.1140C>T · rs137907646 · VCV723906
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.153%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.3 | GERP -2.1 |
| Overall | ||
| CADD | 5.472 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.153%
Admixed American · 92/60,028 alleles
Filtering AF
0.128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.118%
Overall
0.00886%
143/1,613,664 alleles · rare
exomes 132/1,461,310 · genomes 11/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.153% | 652 |
| Middle Eastern | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| African / African-American | 0.004% | 25,020 |
| European (non-Finnish) | 0.00246% | 40,690 |
| South Asian | 0.0022% | 45,543 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SPHK2
- Protein
- p.Pro380=
- Coding
- c.1140C>T
- MANE Select
- NM_020126
- dbSNP
- rs137907646
- Type
- single nucleotide variant
- Location
- chr19:48628948 (GRCh38)
- Gene constraint
- LOEUF 0.934 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.65
Similar variants
- SPHK2 p.Ala506Ser Benign ★★ same type
- SPHK2 p.Asp530Glu Likely benign ★★ same type
- SPHK2 p.Ala141Ser Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala141Val Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala281Thr Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala295Val Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala367Thr Uncertain significance ★ ⚠ same type
- SPHK2 p.Ala38Thr Uncertain significance ★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sphk2-p-pro380 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown